Colorants allow easy coloring
to make capsules more distinguishable
and appealing.

Mixing with crystallized
gelatin prevents capsules from sticking
together or to a container, and also prevents
delayed dissolution of the capsules.

Moisture content of the
capsule shells is reduced to 7 〜 9%. Generally,
moisture content that is too low could
lead to the tendency for cracking and
too high a moisture content could cause
problems such as sticking.

Enteric coating enables
absorption in the intestinal tract.

Drug
substances that are naturally in an oil
phase

Oil
phase drug substances that are diluted with
an oily base

Oil-soluble drug substances that are dissolved
in an oily base

Water-soluble
drug substances that are dissolved in an
aqueous base (Macrogol 400)

Drug
substances that are suspended in an oily
base

High gas barrier properties
of the capsule shell protect stability of
drug substances against oxidation

Treatment of the capsule
shell with titanium oxide for protection
against light supports stability of drug
substances.

Compounds that
are active at trace amounts, such as alfacalcidol,
can be injected uniformly on an μg scale.

Compounds that cannot be processed
into tablet form due to their relatively
low melting point can be filled as an oil
phase without melting into a soft capsule.

Drug substances in oil phase
or as suspensions lead to higher bioavailability.

Macrogol
400 is used as an aqueous base. If a drug substance
is water soluble, it is either solubilized in
water first and mixed with Macrogol 400, or solubilized
directly in Macrogol 400. Excess water could lead
to problems after the encapsulation process. Drying
process conditions must be adjusted accordingly
when aqueous bases are used.

When a drug substance
is solubilized in an oily base, it becomes clear.
However, when a drug substance is insoluble in
an oily base or its low solubility requires a
large volume of solution, then it is treated as
a suspension. Beeswax or surfactants are used
as a suspension agent for oily bases, and Macrogol
4000 or 6000 is used when Macrogol 400 is the
base.

Surfactants are not
only used as a suspension agent, but also to enhance
solubility and stability. In addition, as an effect
on elution and absorption, surfactants are considered
to be important in the designing of inner fill
material formulation. Polysorbate, glycerin fatty
acid esters, and hydrogenated castor oil are mainly
used.

Regular
range is 50 to 2000mg; however, amounts
beyond this range are also possible.

Sample production can be from as
small a scale as a couple kilograms to the manufacture
of investigational drugs by our Technical Research
Laboratory. During sample production, capsule
shell formulation, fill material formulation,
and data collection at critical steps of the manufacturing
process are performed. We design formulations
customized to the drug substances provided by
our customers.

Stability testing is performed after the final
stage of bottling, PTP, or pillow packaging.
We also perform stability testing and elution
testing upon request.